In recent years fiber-optic chemical sensors have been developed to detect the presence and monitor the concentration of various analytes, including oxygen, carbon dioxide, glucose, inorganic ions, and hydrogen ion, in liquids and in gases. Such sensors are based on the recognized phenomenon that the absorbance and in some cases the luminescence of certain indicator molecules is specifically perturbed in the presence of certain analyte molecules. The perturbation of the luminescence and/or absorbance profile can be detected by monitoring radiation that is absorbed, reflected, or emitted by the indicator molecule when illuminated in the presence of a specific analyte. Fiber-optic probes have been developed that position an analyte-sensitive indicator molecule in a light path that is typically made up of a pair of optical fibers. One fiber transmits electromagnetic radiation from a light source to the indicator molecule; the other fiber transmits the return light from the indicator molecule to a light sensor for measurement. The indicator molecule is typically housed in a sealed chamber whose walls are permeable to the analyte.
For example, the fiber-optic pH probe disclosed in U.S. Pat. No. 4,200,110 includes an ion-permeable membrane envelope which encloses the distal ends of a pair of optical fibers. The envelope is a short section of dialysis tubing which fits closely about the two fibers. A pH-indicating dye-containing solid material, e.g., phenol red/methyl methacrylate copolymer, is packed tightly within the membrane distal to the ends of the fibers. Cement is applied to seal the distal end of the membrane and also the proximal end where the optical fibers enter the membrane. The membrane has pores of a size large enough to allow passage of hydrogen ions while being sufficiently small so as to preclude passage of the dye-containing solid material. The probe operates on the concept of optically detecting the change in color of the pH-sensitive dye, e.g., by monitoring the green (570 nm) intensity of phenol red. One of the fibers is connected at its proximal end to a light source, while the other fiber is connected at its proximal end to a light sensor. Light is backscattered through the dye from one fiber into the other fiber. In preparing the dye-containing material, light scattering polystyrene microspheres of about 1 micron diameter may be added prior to incorporation of the dye material into the hollow membrane. A similarly constructed fiber-optic oxygen probe, employing a fluorescent dye sensitive to oxygen quenching, is disclosed in U.S. Pat. No. 4,476,870.
U.S. Pat. No. 4,344,438 is of interest for disclosing a fiber-optic chemical sensor that employs a single optical fiber. Here again, a short section of dialysis tubing is mounted atop the fiber as an analyte-permeable indicator-containing housing.
Such fiber-optic probes are small enough to pass through a hypodermic needle and flexible enough to be threaded through blood vessels for physiological studies. However, promising medical applications, such as continuous blood gas monitoring, have been hindered because experience has shown that such probes are difficult and expensive to manufacture and calibrate. Each probe must be exactingly constructed by hand under a microscope, a process that requires several hours per probe. Considerable unit-to-unit variability in calibration requirements results from the slight variations in the assembled configuration of the components. The unique signal response of each hand-crafted probe must be calibrated at the time of the assay, typically with at least two reference pH or other analyte concentration values to adequately define the calibration curve.